The overall research goal of this laboratory continue to be the identification, isolation and functional characterization of human T lymphocyte subsets. Our approach is based on the hypothesis that during the ontogeny of T cells, specific differentiation antigens become expressed on functionally unique subsets. During the last grant period, evidence to support this hypothesis has emerged from studies which demonstrated that heteroantibodies raised either by conventional means (TH-1, TH-2) or by hybridoma secreting monoclonal antibodies can be used to isolate and distinguish human helper, suppressor and cytotoxic T lymphocytes. However, formal definition of the cell surface architecture of human T cell sets remains embryonic. The introduction of a single new differentiation antigen which functionally subdivides an already identified subset geometrically increases the details to be unraveled. This grant renewal centers on technical advances made since the preceding award which will allow for more informative and precise studies of human T cell immunobiology. These advances include the production of monoclonal antibodies to human T cell sets, the development of sensitive and quantitative functional techniques for the analysis of human T-B and T-T interactions and the functional capacity to establish long term cultures of highly defined antigen specific human T cell sets. During the next several years, we plan to: 1) continue the development and analysis of monoclonal antibodies which specifically identify functionally distinct human T cell subsets; 2) isolate and functionally characterize individual T cell sets with emphasis on the T-T interactions important in immunoregulation; 3) determine whether the differentiation antigens which distinguish T cell sets are themselves involved in the functions of cells they identify and 4) apply the detailed analysis of T cells to the direct study of patients with putative immunoregulatory abnormalities.